The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles.

PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health.

Estimating optimal thresholds for adherence to RASA medications among older adults with hypertension.

Background: The Centers for Medicare and Medicaid Services (CMS) Star Ratings program incentivizes health plans in Medicare to improve performance on a variety of quality measures such as adherence to renin-angiotensin system antagonists (RASAs). Adherence to RASA medications, defined as having a proportion of days covered (PDC) of at least 80%, has been improving for several years, suggesting that further investigation is needed to assess the appropriateness of the current 80% PDC threshold for medication adherence as an indicator of quality. The 80% PDC threshold has been found to be associated with improved health care resource utilization outcomes; however, little evidence exists to show that this threshold is optimal.

Patient perceptions of their experience with comprehensive medication reviews: A framework for continued quality improvement.

Background: A comprehensive medication review (CMR) is an annual service offered to eligible Medicare Part D beneficiaries as a component of the Medication Therapy Management program. However, little is known about the most meaningful aspect of CMRs from the patient's perspective. This information is necessary to help improve the service.

Machine Learning in Clinical Diagnosis of Head and Neck Cancer.

Objective: Machine learning has been effective in other areas of medicine, this study aims to investigate this with regards to HNC and identify which algorithm works best to classify malignant patients.

Design: An observational cohort study.

Setting: Queen Elizabeth University Hospital.

The frequency and clinical impact of synonymous HTT loss-of-interruption and duplication-of-interruption variants in a diverse HD cohort.

Purpose: To determine the frequency and clinical impact of loss-of-interruption (LOI) and duplication-of-interruption modifier variants of the HTT CAG and CCG repeat in a cohort of individuals with Huntington disease (HD).

Methods: We screened symptomatic HD participants from the UBC HD Biobank and 5 research sites for sequence variants. After variant identification, we examined the clinical impact and frequency in the reduced penetrance range.

Whole genome sequencing enhances molecular diagnosis of primary ciliary dyskinesia.

Background: Primary ciliary dyskinesia (PCD) is a genetic disorder affecting motile cilia. Most cases are inherited recessively, due to variants in >50 genes that result in abnormal or absent motile cilia. This leads to chronic upper and lower airway disease, subfertility, and laterality defects.

Development of covalent chemogenetic K channel activators.

K potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (covalent activation of TREK family K channels to clamp membrane potential) that leverages the discovery of a K modulator pocket site that reacts with electrophile-bearing derivatives of a TREK subfamily small-molecule activator, ML335, to activate the channel irreversibly.

Examining the Psychological Measures and Feasibility of Recreational Trail Rides in Reducing Cravings for Addictive Substances among Veterans: A Replication Pilot Study.

Introduction: Equine-assisted services have been gaining popularity as complementary therapies for a variety of populations with a diversity of diagnoses. Interventions using equines might benefit the military Veteran population through building therapeutic alliance as well as reducing symptoms. This pilot observational study is primarily aimed to investigate safety, feasibility, and acceptability of equine-assisted services for Veterans with substance abuse disorders.

Automated translation accurately translates recorded pediatric neurosurgery clinic conversations between Spanish and English.

Objective: The purpose of this study is to analyze an automated voice to text translation device by reporting the translation accuracy for recorded pediatric neurosurgery clinic conversations, classifying errors in translation according to their impact on overall understanding, and comparing the incidence of these errors in English to Spanish vs. Spanish to English conversations.

Methods: English and Spanish speaking patients at a single academic health system's outpatient pediatric neurosurgery clinic had their conversations recorded.

Early Mobility Index and Patient Outcomes: A Retrospective Study in Multiple Intensive Care Units.

Background: Early mobility interventions in intensive care units (ICUs) are safe and improve outcomes in subsets of critically ill adults. However, implementation varies, and the optimal mobility dose remains unclear.

Objective: To test for associations between daily dose of out-of-bed mobility and patient outcomes in different ICUs.

Type I Diabetes Mellitus Suppresses Experimental Skin Carcinogenesis.

This study explores the previously uncharted territory of the effects of ultraviolet (UV) radiation on diabetic skin, compared to its well-documented impact on normal skin, particularly focusing on carcinogenesis and aging. Employing hairless SKH-hr2, Type 1 and 2 diabetic, and nondiabetic male mice, the research subjected these to UV radiation thrice weekly for eight months. The investigation included comprehensive assessments of photoaging and photocarcinogenesis in diabetic versus normal skin, measuring factors such as hydration, trans-epidermal water loss, elasticity, skin thickness, melanin, sebum content, stratum corneum exfoliation and body weight, alongside photo documentation.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

Background: The ratio of oxygen saturation index (ROX index; or S /F /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD.

Low surgical weight associated with ETV failure in pediatric hydrocephalus patients.

The use of endoscopic third ventriculostomy (ETV) for treatment of pediatric hydrocephalus has higher failure rates in younger patients. Here we investigate the impact of select perioperative variables, specifically gestational age, chronological age, birth weight, and surgical weight, on ETV failure rates. A retrospective review was performed on patients treated with ETV - with or without choroid plexus cauterization (CPC) - from 2010 to 2021 at a large academic center.

Living with type 2 diabetes: A social cognitive perspective on adherence.

Objective: This mixed methods study examines the relationship between outcome expectations, self-efficacy, and self-care behaviors in individuals with type 2 diabetes (T2DM). It also explores the personal values motivating these behaviors through in-depth interviews.

Methods: Adults with T2DM (n = 108, M age = 57 years, 58% female, 48% Black) completed questionnaires and participated in in-depth interviews using a laddering technique.

Nurses' Perceived Effects of Visitor Restrictions in Hospital Maternity Units.

Purpose: To explore how perinatal nurses perceive the effects of visitor restrictions on patient care within a hospital setting.

Study Design And Methods: We distributed a cross-sectional survey online to perinatal nurses in May of 2022. Characteristics of respondents were analyzed using descriptive statistics.

Postconception age at surgery as a predictor of ventriculoperitoneal shunt failure.

Objective: The gold standard of pediatric hydrocephalus management is the ventriculoperitoneal (VP) shunt. However, VP shunts have high failure rates, and both young age and prematurity have been identified as potential risk factors for shunt failure, although neither variable describes total development at the time of surgery. This study aimed to further characterize age and shunt failure through the use of postconception age at surgery (PCAS) as well as investigate the 40-week PCAS threshold initially described in 1999.

Phosphorylation of Syntaxin 4 by the Insulin Receptor Drives Exocytic SNARE Complex Formation to Deliver GLUT4 to the Cell Surface.

A major consequence of insulin binding its receptor on fat and muscle cells is the stimulation of glucose transport into these tissues. This is achieved through an increase in the exocytic trafficking rate of the facilitative glucose transporter GLUT4 from intracellular stores to the cell surface. Delivery of GLUT4 to the cell surface requires the formation of functional SNARE complexes containing Syntaxin 4, SNAP23, and VAMP2.

Characterizing intubation practices in response to the COVID-19 pandemic: a survey of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) sites.

Objective: The risk of occupational exposure during endotracheal intubation has required the global Emergency Medicine (EM), Anesthesia, and Critical Care communities to institute new COVID- protected intubation guidelines, checklists, and protocols. This survey aimed to deepen the understanding of the changes in intubation practices across Canada by evaluating the pre-COVID-19, early-COVID-19, and present-day periods, elucidating facilitators and barriers to implementation, and understanding provider impressions of the effectiveness and safety of the changes made.

Methods: We conducted an electronic, self-administered, cross-sectional survey of EM physician site leads within the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) to characterize and compare airway management practices in the pre-COVID-19, early-COVID-19, and present-day periods.

Development of covalent chemogenetic K channel activators.

K potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (Covalent Activation of TREK family K channels to cLAmp Membrane Potential) that leverages the discovery of a site in the K modulator pocket that reacts with electrophile-bearing derivatives of a TREK subfamily small molecule activator, ML335, to activate the channel irreversibly.

A Pilot Replication Study of Implementing an Equine-Assisted Services Program Within a VA Residential Substance Use Disorder Treatment Program.

Introduction: Veterans have high rates of substance use disorders and other mental health conditions including post-traumatic stress disorder. Effective treatments for these conditions exist; however, high attrition rates and residual symptoms after completing treatment are common. Complementary treatment approaches could enhance treatment engagement and/or response among this population.

Delivery of mutant huntingtin-lowering antisense oligonucleotides to the brain by intranasally administered apolipoprotein A-I nanodisks.

Lowering mutant huntingtin (mHTT) in the central nervous system (CNS) using antisense oligonucleotides (ASOs) is a promising approach currently being evaluated in clinical trials for Huntington disease (HD). However, the therapeutic potential of ASOs in HD patients is limited by their inability to cross the blood-brain barrier (BBB). In non-human primates, intrathecal infusion of ASOs results in limited brain distribution, with higher ASO concentrations in superficial regions and lower concentrations in deeper regions, such as the basal ganglia.

A checklist for a consistent, comprehensive medication review.

Introduction: Medicare Advantage Part D plans and stand-alone Part D prescription drug plans are required by the Centers for Medicare and Medicaid Services to have qualified providers, including pharmacists, and offer annual comprehensive medication reviews (CMRs) for eligible Medicare beneficiaries. Although guidance on the components of a CMR is available, providers have flexibility in how to deliver the CMR to patients and which content to cover. With the variety of patient needs, CMR content is not always consistently delivered in practice.

It is time for a new comprehensive medication review quality measure.

Medication therapy management (MTM) services include comprehensive medication reviews (CMRs), which have been completed with millions of patients since their inception in the United States. The current MTM quality measure focuses on whether CMRs were completed (ie, the CMR completion rate). However, this process measure does not assess quality of care, or patient-reported or other outcomes of CMRs, and, therefore, does not reward MTM providers for improving health outcomes.

The association between social determinants of health and patient-centred outcomes in adults with heart failure with reduced ejection fraction.

Aims: To explore the associations between social determinants of health and patient-centred outcomes among adults with chronic heart failure with reduced ejection fraction.

Design: Cross-sectional online self-report survey.

Methods: A survey assessing social determinants of health (demographics, socio-economic position, affordability of care and social support) and patient-centred outcomes, including the Kansas City Cardiomyopathy Questionnaire-12 and validated measures of medication adherence, treatment satisfaction, treatment burden and mental health, was completed by 512 adults with chronic heart failure with a reduced ejection fraction between 06 March and 29 June 2020.